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is a significant concern for physicians. Central
( y! x( O1 @: F$ y: V* s: _: mprecocious puberty (CPP), which is mediated! h$ N% L4 ?3 j x
through the hypothalamic pituitary gonadal axis, has, s8 D& y) c7 Q9 r, {
a higher incidence of organic central nervous system# Y/ C: Q2 B, }8 m9 ?, R) l
lesions in boys.1,2 Virilization in boys, as manifested. Y( t$ }) ?0 Q7 n$ L, Z e; k
by enlargement of the penis, development of pubic
" i3 _6 X8 p& Jhair, and facial acne without enlargement of testi-8 K' I( K6 z( `( z3 D! B
cles, suggests peripheral or pseudopuberty.1-3 We& u5 j; N1 y/ v* V; A
report a 16-month-old boy who presented with the# \ \# A# E+ ~) ]6 b
enlargement of the phallus and pubic hair develop-
! B' S9 z/ C! ?6 C0 \ment without testicular enlargement, which was due
0 N) j- ?& Q; z& O" ?! dto the unintentional exposure to androgen gel used by# I W$ d! y) G$ t( _! k9 \
the father. The family initially concealed this infor-
' k2 Z& Y2 K' D5 `$ m1 R, Rmation, resulting in an extensive work-up for this6 O: ~ J/ b8 p( J: y& e
child. Given the widespread and easy availability of2 u( p7 t% E& \& g6 ~
testosterone gel and cream, we believe this is proba-9 `- A) i7 U9 s. m- V( A+ n9 m
bly more common than the rare case report in the6 A$ l- v) i/ s) D! b
literature.4- L% T% S8 u7 j E& ]# Y4 ?
Patient Report
0 L4 G, g1 q cA 16-month-old white child was referred to the
2 T. W, D! K9 V5 \/ v1 sendocrine clinic by his pediatrician with the concern
" c$ K% R3 }' O6 n" c+ bof early sexual development. His mother noticed6 V& a! ]! s7 I
light colored pubic hair development when he was2 ?$ Y5 X# g- U" Q7 Y! t
From the 1Division of Pediatric Endocrinology, 2University of
0 n2 o* Y# ~$ h8 F z3 p+ d# j4 BSouth Alabama Medical Center, Mobile, Alabama.; m6 h: ?- z/ D2 V; ^, l5 x
Address correspondence to: Samar K. Bhowmick, MD, FACE,
9 i/ [- ~( i$ t/ kProfessor of Pediatrics, University of South Alabama, College of
0 I- ]* E& C# VMedicine, 2451 Fillingim St. Mastin 212, Mobile, AL 36617-2297;8 @% m+ ~9 O* `% K0 y
e-mail: [email protected].) C' {8 o8 K& s V/ V
about 6 to 7 months old, which progressively became. R ]$ i) ?9 Q7 k& [# x) p1 j$ K
darker. She was also concerned about the enlarge-6 h7 ]' q( `6 b h- W
ment of his penis and frequent erections. The child9 t5 `+ c0 E% |0 r' [
was the product of a full-term normal delivery, with
- f7 c l3 {# [. e% G" h- `a birth weight of 7 lb 14 oz, and birth length of
- P9 S1 Z r; E/ _6 P$ k20 inches. He was breast-fed throughout the first year
" ?: D7 W7 _4 Oof life and was still receiving breast milk along with! R/ I* ~& K. i
solid food. He had no hospitalizations or surgery,- i% h! V+ E7 L; I4 r! t
and his psychosocial and psychomotor development
. {- ^' k; g+ w3 a7 Xwas age appropriate.% |2 u: O1 g+ a" i7 L
The family history was remarkable for the father,
. e( S, D2 d: \, \1 Kwho was diagnosed with hypothyroidism at age 16, g& ]. w+ r! |# p9 A- |
which was treated with thyroxine. The father’s0 y7 S# \) N* l
height was 6 feet, and he went through a somewhat+ N1 B: d m" q
early puberty and had stopped growing by age 14.$ x3 f) W1 ~& h5 _! n, g+ ]1 I+ H
The father denied taking any other medication. The0 o3 ?' `! N( n+ k
child’s mother was in good health. Her menarche% d+ }$ N& p" p1 Z. C# b
was at 11 years of age, and her height was at 5 feet
. g% l% w2 a* ~$ {5 inches. There was no other family history of pre-
5 ~2 e/ k/ E/ m. n5 vcocious sexual development in the first-degree rela-% ~" w# \; W. a8 f6 N
tives. There were no siblings.
/ }& t% J2 F; G8 q3 e2 jPhysical Examination/ C' M# n3 n8 @# B. O$ k: R
The physical examination revealed a very active,
0 Z. i/ N `3 t$ {; @. r6 z# p3 @playful, and healthy boy. The vital signs documented) ^2 \! k; H* x1 c
a blood pressure of 85/50 mm Hg, his length was, g( L. Y+ D! G% e5 p
90 cm (>97th percentile), and his weight was 14.4 kg
. {8 A" ^$ i& N( \(also >97th percentile). The observed yearly growth
# h: C* \& F5 P& ^5 u7 `8 ]% @9 |/ @, Hvelocity was 30 cm (12 inches). The examination of6 N0 R$ v2 {, y6 L% P
the neck revealed no thyroid enlargement.
0 D7 w; K6 C8 e& [# j* ]8 G9 {The genitourinary examination was remarkable for
) y0 i3 j& V4 V) fenlargement of the penis, with a stretched length of# Y$ j4 \' y$ f4 A6 s, V- q
8 cm and a width of 2 cm. The glans penis was very well3 U" m4 _9 k4 Q; C6 g$ O" x, `
developed. The pubic hair was Tanner II, mostly around2 y8 F# p; R# u& G" ~7 \1 M
5403 G: b U% h' \5 t/ j0 Q: |% K
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
3 `' O3 u. a8 J6 `the base of the phallus and was dark and curled. The$ `3 |8 C0 g* r+ L x9 Q+ T2 j+ V
testicular volume was prepubertal at 2 mL each.
6 D( T W/ v8 j; eThe skin was moist and smooth and somewhat
# c- {3 d& R& L$ L3 Moily. No axillary hair was noted. There were no
1 E9 w% H8 T# o3 t+ b [abnormal skin pigmentations or café-au-lait spots.5 L' q: |! n! U$ E2 s
Neurologic evaluation showed deep tendon reflex 2+
* l& D. `* l# P0 Z9 Ubilateral and symmetrical. There was no suggestion
/ h' h q$ A |' _3 `of papilledema.
) t/ C- f+ Y$ y: k4 E+ XLaboratory Evaluation
8 a% f3 n ^( j6 |The bone age was consistent with 28 months by
2 `1 z& I0 O$ \ M& o3 q7 uusing the standard of Greulich and Pyle at a chrono-
; P4 }2 x8 y+ e& ?! b: glogic age of 16 months (advanced).5 Chromosomal
/ B0 G$ C1 l$ f5 F1 Nkaryotype was 46XY. The thyroid function test
+ O/ B. w4 n% `$ r1 D- bshowed a free T4 of 1.69 ng/dL, and thyroid stimu-6 q! @7 i6 ~9 W# w
lating hormone level was 1.3 µIU/mL (both normal).$ K( h. [( A: j2 {
The concentrations of serum electrolytes, blood
; X$ E$ m+ Y+ O7 o! U. w3 j# T: Yurea nitrogen, creatinine, and calcium all were
8 e! ]+ y! S. s5 G- mwithin normal range for his age. The concentration5 f* w0 z% a9 ^& A8 h! t+ x# G& ~
of serum 17-hydroxyprogesterone was 16 ng/dL% w3 G8 `2 Q h
(normal, 3 to 90 ng/dL), androstenedione was 20
1 q+ m' F* M0 I- ^- A! _% ^; Y9 kng/dL (normal, 18 to 80 ng/dL), dehydroepiandros-
/ d3 x7 N. ^ y9 f% mterone was 38 ng/dL (normal, 50 to 760 ng/dL),) r/ ^! b" Q6 \: |
desoxycorticosterone was 4.3 ng/dL (normal, 7 to X9 A! L5 Q4 a0 P) B
49ng/dL), 11-desoxycortisol (specific compound S)
/ e* \9 {/ ?! W, j3 s: cwas 43 ng/dL (normal, 10 to 156 ng/dL), serum cor-1 C/ D2 @+ L4 \8 H/ Y
tisol was 7.6 µg/dL (normal, 2.8 to 23 µg/dL), total M3 a7 p4 l, l: I
testosterone was 60 ng/dL (normal <3 to 10 ng/dL),4 M! ?& \$ U( o' m
and β-human chorionic gonadotropin was less than- z9 u5 o. o8 V/ c0 V& o
5 mIU/mL (normal <5 mIU/mL). Serum follicular* z6 y# @" S9 B; Q' L0 E: k* l% Z! U
stimulating hormone and leuteinizing hormone* g1 m' @9 h1 @* M7 ?9 m" E
concentrations were less than 0.05 mIU/mL4 X0 f6 l0 w! b
(prepubertal).
( l7 ~+ W1 }! n7 ]4 D$ YThe parents were notified about the laboratory+ B; B. g: o: w3 F0 B0 ~
results and were informed that all of the tests were
3 a" I, I) T5 f1 m! Z2 z2 Rnormal except the testosterone level was high. The2 [7 R8 v* `7 C2 S
follow-up visit was arranged within a few weeks to7 d5 C! ~; }' S; E _
obtain testicular and abdominal sonograms; how-
2 I* k. p, _" k+ l v5 Y3 V) x/ U+ z% Cever, the family did not return for 4 months.
* u" u+ w# ~! H4 F4 n% Y9 FPhysical examination at this time revealed that the
+ k& D7 G3 k# }+ c6 [child had grown 2.5 cm in 4 months and had gained; o. `; X1 @5 u
2 kg of weight. Physical examination remained
/ t$ b. z: \3 X& Xunchanged. Surprisingly, the pubic hair almost com-
% L4 p. }3 L; @pletely disappeared except for a few vellous hairs at
- h2 H7 u5 E% n) I6 Z0 O# wthe base of the phallus. Testicular volume was still 2
0 V* N9 m* V% y- W _: ]mL, and the size of the penis remained unchanged.
# V$ u5 l* T- c4 k0 r- x$ ^The mother also said that the boy was no longer hav-/ v( T& y* G' {, Z, p5 {
ing frequent erections.
3 B. a& Q) {6 n5 JBoth parents were again questioned about use of
: H6 Y0 L4 I' X( t. i& lany ointment/creams that they may have applied to8 g' g- a# D/ @7 N5 A- p
the child’s skin. This time the father admitted the
' }6 o6 Q- i n. x& ]6 VTopical Testosterone Exposure / Bhowmick et al 541
) l. m) y% J4 N# O+ Q: t7 {" Vuse of testosterone gel twice daily that he was apply-- v( h8 m( k+ M; t0 k
ing over his own shoulders, chest, and back area for
8 q* w' S9 ?6 S8 ga year. The father also revealed he was embarrassed" {+ } m$ ^. M( V
to disclose that he was using a testosterone gel pre-' q" `3 a! A; U( Q8 N0 |
scribed by his family physician for decreased libido2 p* p2 ]2 u- w) J
secondary to depression.
" s8 |2 U6 W7 g: q) }+ B! Q- PThe child slept in the same bed with parents.+ `7 `. y6 f' d6 n/ X
The father would hug the baby and hold him on his
* B: K C$ n! j; J, Fchest for a considerable period of time, causing sig- @$ }" S; I |0 r5 C/ Z2 J
nificant bare skin contact between baby and father.( c0 L2 A" e* Y( c, \
The father also admitted that after the phone call,
3 c. K z% k' C8 S- {$ @when he learned the testosterone level in the baby1 E) t4 D0 Z$ v$ I
was high, he then read the product information5 ~! y: x3 J5 C$ u: u! ]. C
packet and concluded that it was most likely the rea-$ D, d' b- I0 v1 U
son for the child’s virilization. At that time, they
5 x( _- r2 C [7 h7 c. xdecided to put the baby in a separate bed, and the1 w2 \" f/ G) n
father was not hugging him with bare skin and had
7 H V2 C1 _& H9 w* l" D0 W+ {been using protective clothing. A repeat testosterone( x1 z4 Q. \ B) T d# Y$ E
test was ordered, but the family did not go to the* p- z; p" u5 K0 d& T
laboratory to obtain the test.
1 |9 {8 ]: \9 e$ V; P% ODiscussion
3 v; {' v) ?9 iPrecocious puberty in boys is defined as secondary
' |( }9 r" r) {7 t* o: ?sexual development before 9 years of age.1,4
4 a! _/ ~$ u* ePrecocious puberty is termed as central (true) when
3 B" |! g& J2 R& h2 Ait is caused by the premature activation of hypo-3 P/ {0 N+ T( J) ]4 s, A/ X$ v$ |
thalamic pituitary gonadal axis. CPP is more com-! Y4 N0 q0 J# A; a
mon in girls than in boys.1,3 Most boys with CPP( t/ x' ]3 M- e u$ I
may have a central nervous system lesion that is0 c2 b- q d7 R" P u9 c
responsible for the early activation of the hypothal-
' s; M, u5 U6 d( i Kamic pituitary gonadal axis.1-3 Thus, greater empha-* _8 D( J5 Y- D1 _
sis has been given to neuroradiologic imaging in; }9 t; s- Y# `0 r' x
boys with precocious puberty. In addition to viril-
5 m. l. m/ U. m% mization, the clinical hallmark of CPP is the symmet-- |/ L( q1 a% t+ A
rical testicular growth secondary to stimulation by% j {& M8 f& G+ w* c8 B; N1 O% c
gonadotropins.1,33 v6 f+ r- I) A7 d
Gonadotropin-independent peripheral preco-
& g; Y' _' X2 ] Q7 xcious puberty in boys also results from inappropriate& r/ ]% o( u. r, @
androgenic stimulation from either endogenous or
) h7 `% T: v2 x$ ]exogenous sources, nonpituitary gonadotropin stim-8 r; _% N3 H; ^! Q: `
ulation, and rare activating mutations.3 Virilizing; r8 E, b. S A3 B+ a
congenital adrenal hyperplasia producing excessive9 D- V, \) F3 I
adrenal androgens is a common cause of precocious$ D7 I/ S6 e* U5 [& m8 T3 U
puberty in boys.3,46 g/ c) ]; r% I" C! Z7 o
The most common form of congenital adrenal. G* {' Y- K* [! m! ?! B
hyperplasia is the 21-hydroxylase enzyme deficiency.
% ~+ \# e+ i: C$ sThe 11-β hydroxylase deficiency may also result in7 @" {- F% B& N: C' g( o3 k! `, E
excessive adrenal androgen production, and rarely,
- v n. I& U' q7 lan adrenal tumor may also cause adrenal androgen
# u o: J9 X% c7 Uexcess.1,3. V# W" c" C# ^2 b2 L. v
at University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from; \5 y/ H: L8 a' U
542 Clinical Pediatrics / Vol. 46, No. 6, July 2007
+ [ \; x( q4 `* pA unique entity of male-limited gonadotropin-+ d( q" ?/ [8 M2 W( g
independent precocious puberty, which is also known3 b4 c. r' h8 u4 b
as testotoxicosis, may cause precocious puberty at a
' v) t+ T+ L" Y& ^ G8 Jvery young age. The physical findings in these boys
3 l$ f' ]' C& I# E) z- D+ n& {with this disorder are full pubertal development,
$ e/ f/ v6 F+ I' M- ]including bilateral testicular growth, similar to boys' Z6 C5 f& l0 z# u. \+ @
with CPP. The gonadotropin levels in this disorder! s0 V* Q! C" N1 T$ ]& Y6 [- S8 o/ R3 p
are suppressed to prepubertal levels and do not show
2 j g; T! h" W5 Opubertal response of gonadotropin after gonadotropin-
9 @$ m# y0 X! k) d/ g; Creleasing hormone stimulation. This is a sex-linked
, H; X& {% |5 i+ Q5 M9 V9 `autosomal dominant disorder that affects only
* W: P8 W' T/ o: o1 C+ v2 dmales; therefore, other male members of the family
) `4 q5 y5 e0 @5 J) ^may have similar precocious puberty.37 o3 {" u- e6 J/ s6 X; W
In our patient, physical examination was incon-! j* ?" p# s- o* L
sistent with true precocious puberty since his testi-0 T: I! H. V ]4 m# d
cles were prepubertal in size. However, testotoxicosis
2 n1 q4 o; t, J+ E vwas in the differential diagnosis because his father3 E7 ~0 N( e$ U
started puberty somewhat early, and occasionally,
1 D0 T$ o8 P& h) e+ C$ ]testicular enlargement is not that evident in the& r/ h" `# x2 e
beginning of this process.1 In the absence of a neg-3 I+ S* j% u: U0 U# @( O( u
ative initial history of androgen exposure, our7 }/ T/ E# F5 b- s# x
biggest concern was virilizing adrenal hyperplasia,
" e; p+ y, X* h8 X* ?/ \4 n1 {. peither 21-hydroxylase deficiency or 11-β hydroxylase, ~3 v3 f( v9 j8 [/ p
deficiency. Those diagnoses were excluded by find-
5 D9 g* N" i Y4 m2 [' {ing the normal level of adrenal steroids.5 ^; ^) W' d9 a7 O9 m
The diagnosis of exogenous androgens was strongly" q2 a4 y0 s8 x# `; g9 Q
suspected in a follow-up visit after 4 months because
" t+ \0 n# ], Y6 @( n) ythe physical examination revealed the complete disap-
4 S& `2 |7 @! n$ U' H$ o3 e/ _pearance of pubic hair, normal growth velocity, and4 F# G, @* ?, Z# F* c8 ^9 d& s; ?! [
decreased erections. The father admitted using a testos-
4 l, ?! y0 Q1 f0 I9 L- sterone gel, which he concealed at first visit. He was
; {' h2 x" x1 r/ c, e2 d: F" y) ousing it rather frequently, twice a day. The Physicians’
1 A2 ] [# k) i7 L# tDesk Reference, or package insert of this product, gel or
5 ~: ^! O5 H9 D1 l7 x6 u- Q+ Ocream, cautions about dermal testosterone transfer to1 N- K6 z3 W. p0 d7 A
unprotected females through direct skin exposure.) Y% P( Y4 {6 X2 B E, J
Serum testosterone level was found to be 2 times the
+ \9 R& @6 k: N3 f+ fbaseline value in those females who were exposed to" {/ \0 X& B( ?" m9 x' J: _% o
even 15 minutes of direct skin contact with their male
2 Y) Q3 l/ Q& K; G1 @5 {partners.6 However, when a shirt covered the applica- N. W- G( ?" [* U6 `
tion site, this testosterone transfer was prevented. K9 I! E) ^9 g4 H* n
Our patient’s testosterone level was 60 ng/mL,
/ n' x) G S# B; `which was clearly high. Some studies suggest that% v# e, c' f; n( }
dermal conversion of testosterone to dihydrotestos-' ?" v5 g5 @7 j! R5 g' s
terone, which is a more potent metabolite, is more
/ J. M6 e5 D% p( c, ]active in young children exposed to testosterone6 {+ _6 c [9 g( ~ G! S
exogenously7; however, we did not measure a dihy-8 r6 u! |. W( h# O1 y6 T! L \2 F. b. B
drotestosterone level in our patient. In addition to/ O5 I. O" w( L8 N" s
virilization, exposure to exogenous testosterone in& v8 `2 A5 X; Y6 `1 [+ S
children results in an increase in growth velocity and
; c; q+ q7 W9 b( gadvanced bone age, as seen in our patient.. z4 U- n% b) L* W4 V0 W' p
The long-term effect of androgen exposure during" A" X6 t) \! q% U9 Y8 S
early childhood on pubertal development and final7 y; s: A7 ~9 Q
adult height are not fully known and always remain, A* A$ G# l1 H( @1 @9 c
a concern. Children treated with short-term testos-
$ k, X* J* L d6 D1 ~ ~terone injection or topical androgen may exhibit some) m" {2 n9 v3 {: u p' n% Y
acceleration of the skeletal maturation; however, after
4 K. z" B0 t% B5 D- p" i1 Gcessation of treatment, the rate of bone maturation
4 O* k; O; d" B, _( P9 cdecelerates and gradually returns to normal.8,91 {, Y: N l+ n j* b/ ^3 ^/ F
There are conflicting reports and controversy
' I. L d5 o- J; |7 m/ d2 K2 U3 Mover the effect of early androgen exposure on adult
$ P9 P: k; W& ~. X, Z* _* }' A3 Bpenile length.10,11 Some reports suggest subnormal
( a# b7 \4 M9 X& m: tadult penile length, apparently because of downreg- f' @/ \+ y, i- u7 C
ulation of androgen receptor number.10,12 However,0 g( j& o1 q4 `, M' E
Sutherland et al13 did not find a correlation between5 T; V! V( T- G! G
childhood testosterone exposure and reduced adult- H$ z3 D" C, |9 R9 O6 f
penile length in clinical studies.
# p9 y; O- t, `1 j4 d2 gNonetheless, we do not believe our patient is
6 L! N7 y! }$ q9 h+ }7 Agoing to experience any of the untoward effects from
7 `& e. ~- w0 ]- z; @testosterone exposure as mentioned earlier because( u" l* ?! q' N% R
the exposure was not for a prolonged period of time.
* x1 q; l$ _$ \4 g/ v$ G* RAlthough the bone age was advanced at the time of" b8 D5 h1 U: U# J* Q" j
diagnosis, the child had a normal growth velocity at
/ T! p( g5 C9 }9 Z, B2 S' }the follow-up visit. It is hoped that his final adult
: A( _, h% K$ f1 p. u t' Nheight will not be affected.4 V5 g; K: I, f' G4 u
Although rarely reported, the widespread avail-
+ P$ y8 l$ }# c' k; |ability of androgen products in our society may$ G; G! D. u9 N5 ]% }4 `
indeed cause more virilization in male or female
5 K- x' Z2 a; d# y0 A- ]children than one would realize. Exposure to andro-, N# o8 _( ~2 I4 K Y
gen products must be considered and specific ques-
9 s0 u3 L: ~5 K- j! ~tioning about the use of a testosterone product or* ~+ A4 c" g9 R
gel should be asked of the family members during
$ }2 n' s e. R& `# Ethe evaluation of any children who present with vir-. Z$ W5 J* B! {& \# L* Y, F' y
ilization or peripheral precocious puberty. The diag-
+ W# d- E4 d+ F* S6 A# W0 P6 Unosis can be established by just a few tests and by
6 V: U. G6 b6 ~4 _5 F( N$ A8 cappropriate history. The inability to obtain such a
0 {) [3 Y$ ]6 _history, or failure to ask the specific questions, may
8 R& K: f6 j2 Kresult in extensive, unnecessary, and expensive4 H! N4 Q) J8 D- A
investigation. The primary care physician should be
* S0 h/ Y: a* Yaware of this fact, because most of these children1 U' Y; X: a" F1 I3 D* R- J
may initially present in their practice. The Physicians’
) L) l n7 h! |; l7 ?6 B) UDesk Reference and package insert should also put a, q% ]' l3 Y5 y' d$ G
warning about the virilizing effect on a male or" }/ M2 o) y8 Z9 |, N
female child who might come in contact with some-
5 B b% U6 S4 X! [3 J/ F0 Y+ w9 uone using any of these products.& x' ?/ { u7 C, Z3 ?3 \
References ?2 c1 @( l- n5 m, t2 h ^
1. Styne DM. The testes: disorder of sexual differentiation. h% c& q0 |7 o" ]9 \
and puberty in the male. In: Sperling MA, ed. Pediatric+ i: Y: T7 j! L1 a' O4 `+ j
Endocrinology. 2nd ed. Philadelphia, PA: WB Saunders;1 n! G2 d. \* Q$ Z, r' i
2002: 565-628.9 N: S0 j& g O; _
2. Rivarola M, Belgorosky A, Mendilaharzu H, et al. Precocious
8 o* ~, u( S0 G3 X, N* T1 T! E; Fpuberty in children with tumours of the suprasellar pineal
/ d7 p, Q, q+ Yat University of Manchester Library on May 25, 2015 cpj.sagepub.com Downloaded from
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areas: organic central precocious puberty. Acta Paediatr.
0 `. W, ^, B9 Y9 K$ m* L+ g z2001;90:751-756./ d5 Z+ p2 w4 _5 P! G1 m9 g* D
3. Lee PA. Puberty and its disorders. In: Lifshitz F, ed.* d+ P6 S( { p# u
Pediatric Endocrinology. 4th ed. New York, NY: Marcel
% U+ j) o) o! w5 BDekker Inc; 2003:211-238.; v3 E( ]. Q1 \( H9 j# h: s! C, f% X
4. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual
$ x1 L, c6 \* X% t& @development in a two-year-old boy induced by topical
0 _# ~: M) N* mexposure to testosterone. Pediatrics. 1999;104:e23.* N1 c' K0 Z) S4 y6 I
5. Greulich WW, Pyle SI, eds. Radiographic Atlas of5 D6 K0 w( C# ^, N4 l1 z1 [
Skeletal Development of the Hand and Wrist. 2nd ed.% i/ H% z/ e/ D
Stanford, CA: Stanford University Press; 1959." g5 o) `2 T7 ?
6. Physicians’ Desk Reference. Androgel 1% testosterone,
9 Z3 |$ H3 r9 A8 }! tUnimed Pharmaceutical Inc. Montvale, NJ: Medical
. g) r7 V& T$ b) D) i# JEconomics Company, Inc; 2004:3239-3241.
+ m% r- i {# b9 N) a7. Klugo RC, Cerny JC. Response of micropenis to topical
" {" ~& p, x7 B. stestosterone and gonadotropin. J Urol. 1978;119:
% f# d J0 p4 F3 C4 F2 v A667-668.9 }) ^1 P- r) u2 B, e
8. Guthrie RD, Smith DW, Graham CB. Testosterone
! m: {& F3 `& r/ S( _7 Gtreatment for micropenis during early childhood. J Pediatr.
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